We have shown that the embryonic rat pancreas organ cultured in the presence of dimethylnitrosamine was converted into morphologically malignant tissue resembling duct cell carcinoma. Nude mice injected with 1 x 10 to the 6th power cells prepared from this malignant tissue developed multiple subcutaneous nodules resembling duct cell carcinoma. In addition we have demonstrated by light microscopy that the process of malignant conversion is multiphasic, and have recognized the appearence of at least one intermediary cell type in this process. We have used this system to develop a model of human pancreas carcinogenesis. Our preliminary results indicate the possibility of preservation of adult human pancreas in organ culture for up to 5 weeks. Addition of dimethylnitrosamine to culture medium improves the preservation of pancreas explants and induces foci of glandular hyperplasia in these explants by the 5th week of culture. It is the purpose of this project to improve the culture conditions for in vitro preservation of adult human pancreas and to study the morphological and ultrastructural (EM) characteristics of the organ-cultured pancreas. It is further purposed to examine sequentially the morphological and ultrastructural alterations of organ-cultured pancreas explants, induced by dimethylnitrosamine and to develop an in vitro model of human pancreatic carcinogenesis, using dimethylnitrosamine or other nitroso compounds as chemical carcinogens.